Throughout this application, various publications are referenced by number. Full citations for these publications may be found listed at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
It is well-established that the incidence of diabetes is rising sharply in the Unites States and worldwide. Despite aggressive efforts to optimize and achieve strict control of hyperglycemia in affected subjects, the leading cause of death in patients with diabetes remains coronary artery disease (70% of all case fatalities).
In persons with coronary artery stenosis, one form of therapeutic intervention involves percutaneous revascularization (angioplasty) (PTCA). Prior registry data demonstrated that between 15-25% of patients undergoing PTCA have a history of diabetes mellitus. Although there have been great strides in the field of cardiovascular medicine in the last 15 years, there has been little done to improve the outcomes of persons with diabetes and atherosclerotic coronary artery disease. This was most recently clearly demonstrated in a number of recent studies (1-3), including the BARI investigations and the studies comparing the NHANES I and NHANES II cohorts. Comparing these two epidemiologic surveys, investigators showed a marked improvement in cardiovascular and rated outcomes for patients without a history of diabetes. There was an overall 21.1% and 12.6% risk reduction in all cause mortality in non-diabetic men and women, respectively. In contradistinction, there was only a 1.2% reduction in all cause mortality for diabetic men, and a surprising 15.2% increase in all cause mortality for diabetic women. Similar to the NHANE epidemiologic surveys, patients with diabetes seem to be a higher risk cohort of patients following PTCA interventions. Another example of the heightened risk of vascular disease in diabetes of medical urgency concerns the response to angioplasty as illustrated by the BARI study in which patients with diabetes displayed poorer results from angioplasty than from bypass surgery largely because of accelerated restenosis. From the results of these studies, the view has emerged that diabetic patients are at a heightened risk for angiographic and clinical restenosis, late myocardial infarction, late mortality, and need for future revascularization procedures. In data retrieved from one of our institutes (Mid America Heart Institute) involving over 25,000 patients, we found that diabetic patients have a nearly two-fold increase in in-hospital mortality following both elective and urgent PTCA interventions. The in-hospital mortality rate was 0.8% compared with 1.4% for non-diabetic and diabetic patients undergoing elective PTCA, respectively; p<0.001. Similarly, the in-hospital morality rate was 6.9% compared with 12.7% for non-diabetic and diabetic patients undergoing PTCA for acute myocardial infarction, p<0.001.